Loss of calpain 3 proteolytic activity leads to muscular dystrophy and to apoptosis-associated IkappaBalpha/nuclear factor kappaB pathway perturbation in mice

Details

Serval ID
serval:BIB_A5C5D601D53E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Loss of calpain 3 proteolytic activity leads to muscular dystrophy and to apoptosis-associated IkappaBalpha/nuclear factor kappaB pathway perturbation in mice
Journal
Journal of Cell Biology
Author(s)
Richard  I., Roudaut  C., Marchand  S., Baghdiguian  S., Herasse  M., Stockholm  D., Ono  Y., Suel  L., Bourg  N., Sorimachi  H., Lefranc  G., Fardeau  M., Sebille  A., Beckmann  J. S.
ISSN
0021-9525 (Print)
Publication state
Published
Issued date
12/2000
Volume
151
Number
7
Pages
1583-90
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 25
Abstract
Calpain 3 is known as the skeletal muscle-specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. It was previously shown that defects in the human calpain 3 gene are responsible for limb girdle muscular dystrophy type 2A (LGMD2A), an inherited disease affecting predominantly the proximal limb muscles. To better understand the function of calpain 3 and the pathophysiological mechanisms of LGMD2A and also to develop an adequate model for therapy research, we generated capn3-deficient mice by gene targeting. capn3-deficient mice are fully fertile and viable. Allele transmission in intercross progeny demonstrated a statistically significant departure from Mendel's law. capn3-deficient mice show a mild progressive muscular dystrophy that affects a specific group of muscles. The age of appearance of myopathic features varies with the genetic background, suggesting the involvement of modifier genes. Affected muscles manifest a similar apoptosis-associated perturbation of the IkappaBalpha/nuclear factor kappaB pathway as seen in LGMD2A patients. In addition, Evans blue staining of muscle fibers reveals that the pathological process due to calpain 3 deficiency is associated with membrane alterations.
Keywords
Animals *Apoptosis Calpain/chemistry/*deficiency/genetics/metabolism Creatine Kinase/metabolism Crosses, Genetic DNA-Binding Proteins/*metabolism Evans Blue Female Fertility Gene Deletion Gene Targeting Genotype *I-kappa B Proteins Male Mice Mice, Knockout Muscle Fibers/enzymology/metabolism/pathology Muscle, Skeletal/enzymology/metabolism/pathology Muscular Dystrophies/*enzymology/genetics/*metabolism/pathology NF-kappa B/*metabolism Phenotype RNA, Messenger/analysis/genetics Sarcolemma/pathology *Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 16:17
Last modification date
20/08/2019 15:10
Usage data